Exploring the Neurobiological Roots of Emotional Behavior in Tryptophan Metabolism: Insights from Novel Kynurenine Aminotransferase Knockout Mice DOI Open Access
Ágnes Szabó, Eleonóra Spekker, Mónika Szűcs

et al.

Published: Sept. 30, 2023

Memory and emotion, fundamental components of our mental existence, are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD). This condition has been linked serotonin (5-HT) metabolism disruptions. Over 95% the 5-HT precursor tryptophan (Trp) is metabolized through Trp-kynurenine (KYN) metabolic pathway, but little known about its role in behavior. Kynurenine aminotransferases responsible for production Trp-KYN metabolite kynurenic acid. The gene aadat codes mitochondrial kynurenine aminotransferase isotype 2. We generated CRISPR/Cas9-induced knockout (kat2−/−) mice examine consequence deletion on negative valence memory, motor function males 8 weeks age compared them their wild-type counterparts. forced swim test showed increased depression-like behaviors transgenic mice. Anxiety memory tests no significant differences. had fewer center field corner entries, shorter ambulation distances, jumping counts open test. Overall, exhibit behavior a learned helplessness model, emotional indifference, deficits. Here we present first evidence that triggers behaviors, uniquely associated with despair experience rather than adverse-conditioned memory. These findings have profound implications, opening avenues further exploration into main causes experience-based depression despair. investigation potential advance understanding these complex conditions pave way improved therapeutic strategies by elucidating relationship between Trp pathogenesis PTSD.

Language: Английский

Exploring the Neurobiological Roots of Emotional Behavior in Tryptophan Metabolism: Insights from Novel Kynurenine Aminotransferase Knockout Mice DOI Open Access
Ágnes Szabó, Eleonóra Spekker, Mónika Szűcs

et al.

Published: Sept. 30, 2023

Memory and emotion, fundamental components of our mental existence, are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD). This condition has been linked serotonin (5-HT) metabolism disruptions. Over 95% the 5-HT precursor tryptophan (Trp) is metabolized through Trp-kynurenine (KYN) metabolic pathway, but little known about its role in behavior. Kynurenine aminotransferases responsible for production Trp-KYN metabolite kynurenic acid. The gene aadat codes mitochondrial kynurenine aminotransferase isotype 2. We generated CRISPR/Cas9-induced knockout (kat2−/−) mice examine consequence deletion on negative valence memory, motor function males 8 weeks age compared them their wild-type counterparts. forced swim test showed increased depression-like behaviors transgenic mice. Anxiety memory tests no significant differences. had fewer center field corner entries, shorter ambulation distances, jumping counts open test. Overall, exhibit behavior a learned helplessness model, emotional indifference, deficits. Here we present first evidence that triggers behaviors, uniquely associated with despair experience rather than adverse-conditioned memory. These findings have profound implications, opening avenues further exploration into main causes experience-based depression despair. investigation potential advance understanding these complex conditions pave way improved therapeutic strategies by elucidating relationship between Trp pathogenesis PTSD.

Language: Английский

Citations

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